Increased intratumoral fluorothymidine uptake levels following multikinase inhibitor sorafenib treatment in a human renal cell carcinoma xenograft model.
Increased intratumoral fluorothymidine uptake levels following multikinase inhibitor sorafenib treatment in a human renal cell carcinoma xenograft model.
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DOI：
10.3892/ol.2013.1459
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发表时间：
2013-09
期刊：
影响因子：
2.9
通讯作者：
Kuge Y
中科院分区：
文献类型：
--
作者：
Murakami M;Zhao S;Zhao Y;Yu W;Fatema CN;Nishijima KI;Yamasaki M;Takiguchi M;Tamaki N;Kuge Y
早期识别肿瘤对索拉非尼治疗的反应对于选择最佳的个性化治疗策略是必不可少的。然而，目前临床上还没有可靠的预测因子。18 F-氟胸苷（18 F-FLT）正电子发射断层扫描（PET）用于评估肿瘤增殖，因为FLT摄取水平反映了胸苷激酶-1（TK-1）活性。因此，本研究确定了FLT是否能够与肿瘤增殖标志物Ki-67相比，评价人肾细胞癌（RCC; A498）异种移植物对索拉非尼治疗的早期肿瘤反应。将携带A498肿瘤的小鼠分配到对照组和索拉非尼治疗组，每天测量肿瘤体积。给药后第3天和第7天，在处死小鼠前2 h注射[甲基-3H（N）]-3′-氟-3 ′-脱氧胸苷（3 H-FLT）。使用相邻肿瘤切片进行3 H-FLT放射自显影（ARG）和Ki-67免疫组织化学（IHC）。在目视评估中，治疗后肿瘤内3 H-FLT摄取水平弥漫性增加，而Ki-67 IHC未观察到显著变化。在治疗后第3天和第7天，肿瘤内3 H-FLT摄取水平显著增加2.7倍和2.6倍，而肿瘤体积和Ki-67指数没有显著变化。因此，治疗后FLT摄入水平增加，这可能表明索拉非尼抑制胸苷酸合成酶（TS）并补偿性上调TK-1活性。
An early identification of the tumor response to sorafenib treatment is indispensable for selecting optimal personalized treatment strategies. However, at present, no reliable predictors are clinically available. 18F-fluorothymidine (18F-FLT) positron emission tomography (PET) is used to assess tumor proliferation, since the FLT uptake level reflects thymidine kinase-1 (TK-1) activity. Thus, the present study determined whether FLT was able to evaluate the early tumor response to sorafenib treatment in a human renal cell carcinoma (RCC; A498) xenograft in comparison with the tumor proliferation marker, Ki-67. Mice bearing A498 tumors were assigned to the control and sorafenib-treated groups and the tumor volume was measured every day. [Methyl-3H(N)]-3′-fluoro-3′-deoxythymidine (3H-FLT) was injected 2 h prior to the sacrifice of the mice on days three and seven following the treatment. 3H-FLT autoradiography (ARG) and Ki-67 immunohistochemistry (IHC) were performed using adjacent tumor sections. In the visual assessment, the intratumoral 3H-FLT uptake level diffusely increased following the treatment, while no significant changes were observed in Ki-67 IHC. The intratumoral 3H-FLT uptake levels significantly increased by 2.7- and 2.6-fold on days three and seven following the treatment, while the tumor volume and Ki-67 index did not significantly change. Thus, an increased FLT uptake level was demonstrated following the treatment, which may indicate the suppression of thymidylate synthase (TS) and the compensatory upregulation of TK-1 activity by sorafenib.
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影响因子：
11.5
作者：
Apisarnthanarax, Smith;Alauddin, Mian M.;Chao, K. S. Clifford
通讯作者：
Chao, K. S. Clifford
DOI：
10.1158/1078-0432.ccr-11-1677
发表时间：
2011-12-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Liu G;Jeraj R;Vanderhoek M;Perlman S;Kolesar J;Harrison M;Simoncic U;Eickhoff J;Carmichael L;Chao B;Marnocha R;Ivy P;Wilding G
通讯作者：
Wilding G
影响因子：
11.2
作者：
Wilhelm, SM;Carter, C;Trail, PA
通讯作者：
Trail, PA
影响因子：
11.2
作者：
Leyton, J;Latigo, JR;Aboagye, EO
通讯作者：
Aboagye, EO
影响因子：
3
作者：
Chang, Yong S.;Adnane, Jalila;Wilhelm, Scott
通讯作者：
Wilhelm, Scott